From: (Samson) Newsgroups: alt.drugs.hard Subject: Dihydrocodeine(again) (wasRe: Getting Codeine/Hydrocod./Oxyc. Date: 6 Apr 1998 14:49:35 GMT In article , (blerk) wrote: [...] > You can turn codeine into morphine and H, but the >reagents isn't the easiest thing to get.. hydrocodone, you could get a >similiar product to heroin (except it is dihydroheroin), which is >about the same potency.. dihydromorphine is not less potent than >morphine for the person who said it was (dihydros with an unchanged >6-OH is slightly more potent). I had a feeling this can of worms would be reopened. Despite the "truism" that saturating the 7,8 bond should increase activity, this is not true in the case of morphine according to pharmacological evidence. Dihydrocodeine is stronger than codeine, dihydromorphine is weaker than morphine -- about as strong as dihydrocodeine. ==================================================================== J Pharmacol Exp Ther 1997 Jun;281(3):1164-1170 Analgesia by dihydrocodeine is not due to formation of dihydromorphine: evidence from nociceptive activity in rat thalamus. Jurna I, Komen W, Baldauf J, Fleischer W Institut fur Pharmakologie und Toxikologie der Universitat des Saarlandes, Homburg/Saar, Germany. Dihydrocodeine is increasingly used in slow-release preparations for the treatment of chronic pain on step 2 of the "analgesic ladder" of the World Health Organization. Dihydrocodeine is suggested to act after O-demethylation to dihydromorphine. To test this possibility, experiments were carried out on rats under urethane anesthesia in which nociceptive activity was evoked by electrical stimulation of afferent C fibers in the sural nerve and recorded from neurons in the ventrobasal complex of the thalamus. Dihydrocodeine administered by intravenous injection reduced the evoked nociceptive activity in a dose-dependent manner. Like morphine, dihydrocodeine was capable of completely suppressing the evoked activity. Maximum depression was caused by 2 mg/kg, and the ED50 is 0.47 mg/kg. Naloxone (0.2 mg/kg) reversed the effect of dihydrocodeine (2 mg/kg). To inhibit O-demethylation of dihydrocodeine to dihydromorphine, metyrapone or cimetidine (50 mg/kg) was injected intraperitoneally 20 min before dihydrocodeine (1 and 2 mg/kg). This failed to markedly reduce the effect of dihydrocodeine. Dihydromorphine injected intravenously also reduced the evoked activity in a dose-dependent way. Maximum depression occurred at a dose of 4 mg/kg, and the ED50 is 0.97 mg/kg. Dihydrocodeine and dihydromorphine were equieffective when administered by intrathecal injection at a dose of 100 microg. It is concluded that dihydrocodeine causes analgesia independent of biotransformation to dihydromorphine. PMID: 9190849, UI: 97334152 ---------- [Excerpts from article] "Dihydrocodeine administered by intravenous injection to rats depressed the nociceptive activity in neurons of the ventrobasal complex of the thalamus that was evoked by electrical stimulation of afferent C fibers in the sural nerve. Like morphine dihydrocodeine suppressed completely this activity when administered at a sufficiently high dose. This dose was 2 mg/kg for dihydrocodeine ...and 0.5 mg/kg for morphine... [[dhc = 1/4 morphine *maximal* effect]]. The ED50 of dihydrocodeine was ...is 0.47 mg/kg and thus 10 times higher than than that of morphine... (0.044 mg/kg)...[[*minimal* effect]] "Dihydrocodeine (2 mg/kg) injected intravenously was as effective in depressing nociceptive activity evoked in thalamic neurons as dihydromorphine (4 mg/kg) administered by the same route, and the ED50 of dihydrocodeine (0.47 mg/kg i.v) is about half that of dihydromorphine (0.97 mg/kg i.v)... "Dihydrocodeine and dihydromorphine were equieffective when administered by intrathecal injection at a dose of 100 ug... the duration of the effect of dihydrocodeine (100 ug) was significantly shorter than that of dihydromorphine (100 ug)... It is worth noting in this context that morphine and dihydrocodeine are capable of producing a maximum depression of < 50% to 60% of this activity when administered by intrathecal injection [[vs 100% when given i.v]]. This means that maximum analgesia cannot be established from spinal cord alone but results only when all levels of the nociceptive system are acted on by the opioids. "Finally, one cannot neglect the suprising result that dihydrocodeine is more effective than dihydromorphine... because masking the phenolic hydroxyl group (position 3) by the addiction of an alkyl (e.g codeine) or a glucuronic acid residue (eg, morphine-3-glucunoride) generally reduces the analgesic effectiveness or the affinity for mu receptors of morphine. Removal of the double bond between position 7 and 8, however, causes a change in the molecular configuration that might contribute to the increase in analgesic effectiveness of hydromorphone compared with morphine and... dihydrocodeine compared with codeine. The impact of the constitutional change in the opioid molecules on the activation of the opioid receptors will need clarification."